New clathrin-based nanoplatforms for magnetic resonance imaging

Area of Science:

• Biotechnology
• Nanotechnology
• Neuroimaging

Background:

• Magnetic Resonance Imaging (MRI) has limitations in central nervous system (CNS) molecular target visualization due to low sensitivity.
• Developing novel MRI contrast agents is crucial for non-invasive molecular brain imaging.

Purpose of the Study:

• To engineer novel CNS contrast media using bio-nanotechnology based on clathrin proteins.
• To investigate clathrin nanoplatforms for enhanced MRI sensitivity and blood-brain barrier (BBB) penetration.

Main Methods:

• Designed clathrin triskelia and self-assembled clathrin cages as nanocarriers for gadolinium chelates.
• Characterized nanoplatforms for size, structure, protein concentration, and gadolinium content.
• Evaluated relaxivity and BBB crossing capabilities of fluorescent-tagged clathrin nanoplatforms in vivo.

Main Results:

• Clathrin cages demonstrated significantly higher ionic (81 mM⁻¹s⁻¹) and molecular (31,512 mM⁻¹s⁻¹) relaxivity compared to existing agents.
• Clathrin nanoplatforms (triskelia and cages) successfully crossed or bypassed the BBB via intranasal, intravenous, and intraperitoneal routes without enhancers.
• Developed nanoplatforms exhibited high gadolinium loading capacities.

Conclusions:

• Clathrin triskelia and cages represent a novel, biocompatible protein-based nanotechnology for CNS contrast media.
• These nanoplatforms possess suitable physicochemical properties for further in vivo imaging and drug delivery studies.
• Clathrin nanoplatforms offer a promising alternative to current CNS bio-nanotechnologies for molecular brain imaging.